FUZEON SIDE EFFECTS

Last updated on MDtodate: 10/6/2022

SIDE EFFECTS

The following adverse reactions are discussed in greater detail in other sections:

• Administration with Biojector® 2000
• Hypersensitivity Reactions
• Pneumonia

Clinical Trials Experience

Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice.

The overall safety profile of FUZEON is based on 2131 subjects who received at least 1 dose of FUZEON during various clinical trials. This includes 2051 adults, 658 of whom received the recommended dose for greater than 48 weeks, and 63 pediatric subjects.

Assessment of treatment-emergent adverse events is based on the pooled data from the two randomized, controlled, open-label, multicenter trials in treatment-experienced subjects, T20-301 (TORO 1) and T20-302 (TORO 2).

Local Injection Site Reactions

Local injection site reactions were the most frequent adverse events associated with the use of FUZEON. In T20-301 and T20-302, 98% of subjects had at least one local injection site reaction (ISR). A total of 7% of subjects discontinued treatment with FUZEON because of ISRs (4%) or difficulties with injecting FUZEON (3%) such as injection fatigue and inconvenience. Eighty-five percent of subjects experienced their first ISR during the initial week of treatment; ISRs continued to occur throughout treatment with FUZEON. For most subjects the severity of signs and symptoms associated with ISRs did not change during the 48 weeks of treatment. The majority of ISRs were associated with erythema, induration, the presence of nodules or cysts, and mild to moderate pain at the injection site (Table 2). In addition, the average duration of individual ISRs was between three and seven days in 41% of subjects and more than seven days in 24% of subjects. Also, the numbers of ISRs per subject at any one time was between six to 14 ISRs in 26% of subjects and more than 14 ISRs in 1.3% of subjects. Infection at the injection site (including abscess and cellulitis) was reported in 1.7% of adult subjects.

Table 1 : Summary of Individual Signs/Symptoms Characterizing Local Injection Site Reactions to Enfuvirtide in Studies T20-301 and T20-302 Combined (% of Subjects) Through 48 Weeks

Event Category	N=663
	Any Severity Grade	% of Subjects with Grade 3 Reactions	% of Subjects with Grade 4 Reactions
Pain/Discomforta	96%	11%	0%
Induration	90%	39%	18%
		>25 but <50 mm	≥50 mm
Erythema	91%	22%	10%
		>50 but <85 mm	>85 mm
Nodules and Cysts	80%	23%	0.2%
		>3 cm average diameter	Draining
Pruritusb	65%	3%	NA
Ecchymosis	52%	5%	2%
		>3 but ≤5 cm	>5 cm
aGrade 3 = severe pain requiring prescription non-topical analgesics or limiting usual activities. Grade 4 = severe pain requiring hospitalization or prolongation of hospitalization, resulting in death, or persistent or significant disability/incapacity, or life-threatening, or medically significant. bGrade 3 = refractory to topical treatment or requiring oral or parenteral treatment. Grade 4 = not applicable.

 

Other Adverse Events

In T20-301 and T20-302, after study week 8, subjects on background alone who met protocol defined criteria for virological failure were permitted to revise their background regimens and add FUZEON. Exposure on FUZEON+background was 557 patient-years, and to background alone 162 patient-years. Due to this difference in exposure, safety results are expressed as the number of patients with an adverse event per 100 patient-years of exposure. For FUZEON+background, adverse events are also displayed by percent of subjects.

The events most frequently reported in subjects receiving FUZEON+background regimen, excluding ISRs, were diarrhea (38 per 100 patient-years or 31.7%), nausea (27 per 100 patient-years or 22.8%), and fatigue (24 per 100 patient-years or 20.2%). These events were also commonly observed in subjects that received background regimen alone: diarrhea (73 per 100 patient-years), nausea (50 per 100 patient-years), and fatigue (38 per 100 patient-years).

Treatment-emergent adverse events, regardless of causality and excluding ISRs, from Phase 3 studies are summarized for adult subjects, in Table 3. Any Grade 2 or above events occurring at ≥2 percent of subjects and at a higher rate in subjects treated with FUZEON are summarized in Table 3; events that occurred at a higher rate in the control arms are not displayed.

Rates of adverse events for subjects who switched to FUZEON after virological failure were similar.

Table 2 : Rates of Treatment-Emergent Adverse Events* (≥Grade 2) Reported in ≥2% of Subjects Treated with FUZEON** (Pooled Studies T20-301/T20-302 at 48 Weeks)

Adverse Event (by System Organ Class)	FUZEON+ Background Regimen (N=663)	FUZEON+ Background Regimen (N=663)	Background Regimen (N=334)
	663 subjects total	557 total patient-years	162 total patient-years
	% frequency	rate/100 patient-years	rate/100 patient-years
Weight Decreased	6.6%	7.9	6.2
Sinusitis	6.0%	7.2	4.9
Abdominal Pain	3.9%	4.7	3.7
Cough	3.9%	4.7	2.5
Herpes Simplex	3.5%	4.1	3.7
Appetite Decreased	3.2%	3.8	2.5
Pancreatitis	3.0%	3.6	2.5
Pain in Limb	2.9%	3.4	3.1
Pneumonia (see text below)	2.7%	3.2	0.6
Myalgia	2.7%	3.2	1.2
Influenza-Like Illness	2.4%	2.9	1.9
Folliculitis	2.4%	2.9	2.5
Anorexia	2.3%	2.7	1.9
Dry Mouth	2.1%	2.5	1.9
Conjunctivitis	2.0%	2.3	1.9
*Excludes Injection Site Reactions **Events listed occurred more frequently in subjects treated with FUZEON (based on rates/100 patient-years).

 

Less Common Events

The following adverse events have been reported in 1 or more subjects; however, a causal relationship to FUZEON has not been established.

Immune System Disorders: worsening abacavir hypersensitivity reaction

Renal and Urinary Disorders: glomerulonephritis; tubular necrosis; renal insufficiency; renal failure (including fatal cases)

Blood and Lymphatic Disorders: thrombocytopenia; neutropenia; fever; lymphadenopathy

Endocrine and Metabolic: hyperglycemia

Infections: sepsis; herpes simplex

Nervous System Disorders: taste disturbance; Guillain-Barre syndrome (fatal); sixth nerve palsy; peripheral neuropathy

Cardiac Disorders: unstable angina pectoris

Gastrointestinal Disorders: constipation; abdominal pain upper

General: asthenia

Hepatobiliary Disorders: toxic hepatitis; hepatic steatosis

Investigations: increased amylase; increased lipase; increased AST; increased GGT; increased triglycerides

Psychiatric Disorders: insomnia; depression; anxiety; suicide attempt

Respiratory, Thoracic, and Mediastinal Disorders: pneumopathy; respiratory distress; cough

Skin and Subcutaneous Tissue Disorders: pruritus

Laboratory Abnormalities

Table 3 shows the treatment-emergent laboratory abnormalities that occurred in at least 2 subjects per 100 patient-years and more frequently in those receiving FUZEON+background regimen than background regimen alone from T20-301 and T20 302.

Table 3 : Treatment-Emergent Laboratory Abnormalities in ≥2% of Subjects Receiving FUZEON* (Pooled Studies T20-301 and T20-302 at 48 Weeks)

Laboratory Parameters	Grading	FUZEON+ Background Regimen (N=663)	FUZEON+ Background Regimen (N=663)	Background Regimen (N=334)
		663 subjects total	557 total patient-years	162 total patient-years
		% frequency	rate/100 patient-years	rate/100 patient-years
Eosinophilia
1-2 X ULN (0.7 x 109/L)	0.7-1.4 x 109/L	9.1%	10.8	3.7
>2 X ULN (0.7 x 109/L)	>1.4 x 109/L	1.8%	2.2	1.8
ALT
Grade 3	>5-10 x ULN	4.1%	4.8	4.3
Grade 4	>10 x ULN	1.2%	1.4	1.2
Creatine Phosphokinase (U/L)
Grade 3	>5-10 x ULN	6.9%	8.3	8.0
Grade 4	>10 x ULN	2.6%	3.1	8.6
*Events listed occurred more frequently in subjects treated with FUZEON (based on rates/100 patient-years).

 

Adverse Events In Pediatric Patients

FUZEON has been studied in 63 pediatric subjects 5 through 16 years of age with duration of FUZEON exposure ranging from 1 dose to 134 weeks. Adverse experiences seen during clinical trials were similar to those observed in adult subjects, although infections at site of injection (cellulitis or abscess) were more frequent in adolescents than in adults, with 4 events occurring in 3 of 28 (11%) subjects.

Postmarketing Experience

The following adverse reaction has been identified during post approval use of FUZEON. Because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure.

Skin And Subcutaneous Tissue Disorders

Cutaneous amyloidosis at the injection site.